Current estimates indicate that about a third of the world's population is infected with M. tuberculosis, 8.7 million individuals develop the disease annually, and almost 2 million die each year from the disease. Tuberculosis control programs are threatened by the emergence and transmission of multidrug resistant (MDR) and extensively drug resistant (XDR) tuberculosis since the treatment of these cases is more complex, more costly, and frequently less successful than the treatment of drug sensitive strains. The goals of this proposed Program Project are to conduct a series of linked interdisciplinary research projects focused on the emergence and transmission of multidrug and extensively drug resistant tuberculosis and to support these projects through the development of a central core for administration and leadership, database management and a central M. tuberculosis isolate archive. Linked research projects include: a cohort study of host and microbial factors associated with the emergence and transmission of drug sensitive and resistant TB in Lima, Peru;a study designed to characterize M. tuberculosis strain diversity and its contribution to the emergence and spread of MDR;and a study to use epidemic and individual predictive models to support public health policy and clinical decision making for MDR and XDR tuberculosis.